Temperature sensitivity of vinblastine-induced tubulin polymerization in the presence of microtubule-associated proteins

Veena Prasad, Mary Ann Jordan, Richard F. Ludueña

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Abstract

The antitumor drug vinblastine has been a useful probe for examining the interaction of tubulin with the microtubule-associated proteins (MAPs), specifically with τ and MAP 2. Although τ and MAP 2 can stimulate microtubule assembly in vitro, their specific interactions with tubulin are known to differ. For example, in the presence of vinblastine, both τ and MAP 2 cause tubulin to form spirals, but τ causes formation of clustered spirals of high turbidity, while MAP 2 causes formation of loose spirals of low turbidity [Ludueña et al., J. Biol. Chem.259, 12890-12898 (1984)]. Although cold temperatures can inhibit microtubule assembly, cold has no effect on vinblastine-induced tubulin spiral formation. Consequently, we used the vinblastine-tubulin system to examine the interactions of τ and MAP 2 with tubulin at low temperatures. We found that τ-tubulin-vinblastine complexes form about as well at 0°C as at 37°C. In contrast, MAP 2-tubulin-vinblastine complexes form much less well at 0°C than at 37°C. We find, however, that MAP 2, at 0°C, will strongly inhibit, and even reverse, formation of the τ-tubulin-vinblastine complex. This suggests that the temperature-sensitive factor is the MAP 2-stimulated tubulin-tubulin interaction rather than the MAP 2-tubulin interaction per se; this raises the possibility that the tubulin-tubulin interactions stimulated by τ differ in their temperature sensitivity from those stimulated by MAP 2.

Original languageEnglish (US)
Pages (from-to)509-515
Number of pages7
JournalJournal of Protein Chemistry
Volume11
Issue number5
DOIs
StatePublished - Oct 1 1992

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Keywords

  • Vinblastine
  • microtubule-associated proteins
  • microtubules
  • tubulin
  • τ

ASJC Scopus subject areas

  • Biochemistry

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